Postdoctoral Associates

Dr. Ivan Mikhaylov

Graduate & Undergraduate Students

Gregory Shinaberry

Justin Reyes

Joshua Townsend

The group of Alexander Balaeff invites talented graduate and undergraduate students to join our efforts in molecular modeling and discovery. Come study the mysteries of the coolest molecules on Earth, spin molecular machines, run current along DNA wires, or even design a molecular wonder that Mother Nature herself has not designed yet! All without leaving the seat in front of your computer. If interested, e-mail Alexander.Balaeff@ucf.edu.

Research

The research theme of the group can be broadly defined as study and design of biomolecular and biomimetic molecular assemblies. We conduct such studies using a variety of molecular modeling and simulation techniques. Below, we describe the ongoing research projects, including recent and notable results.

DNA Origami etc.

We model 3D "origami" structures folded from multiple DNA strands. Multiple (and wondrous!) DNA origami have been produced in experiment, but little is known about their in-solvent dynamics under room temperature and mechanical properties (defined by the DNA structure and dynamics on the base-pair level, including deviations from the canonical Watson-Crick structure). We work to fill those gaps. Of special interest are the electronic properties of DNA origami. Can the conductive properties of DNA be harnessed to turn the DNA origami into self-assembling nanoscale electronic circuits? (read: the DNA computer?) The jury is out on that one!

We currently work on understanding the dynamic and electronic properties of the DNA cube (shown on the left in the picture above), and the double-crossover DNA structures (right) which can give rise to the DNA "cross" (center), as well as more complex structures, including 2D and 3D lattices of various geometries.

Multiscale Modeling of Biomolecular Assemblies

Biological macromolecules (proteins, RNA) have been designed by Nature to function as complex nanoscale machines performing a variety of chemical and mechanical tasks, such as biosynthesis, molecular transport, and cell locomotion. It is a challenging and exciting task to understand the work of biomolecular machines down to the finest detail and to learn to design similar machines for performing the tasks that we the humans demand! Examples include mass production of biomimetic materials, fighting diseases on the nanoscale, and designing whole new organisms fit for survival in harsh conditions.

The work of a biomolecular machine involves events on multiple temporal and spatial scales. Thus, a multi-scale approach is required to model the work of such machines. Our models combine quantum mechanical calculations, all-atom molecular dynamics simulations, and coarse-grained models such as those based on the theory of elasticity.

The pictures above show our multi-scale models of the molecular complexes of (i) a DNA loop and the lac repressor protein (left) and (ii) the DNA loop, the lac repressor, and the CAP protein (right). The models revealed the structure of the DNA loop bent by the lac repressor, showed how the CAP protein can fit within that loop (resulting in a change of the loop topology!), and described the effect of the forces from the bent loop on the structure and dynamics of the lac repressor.

Molecular Electronics

From DNA origami to PNA monolayers (pictured above), we are interested in the ways and mechanisms of electric charge transfer through biological molecules. Such mechanisms are anything but trivial and are often affected by myriad factors such as molecular sequence and structure, environmental conditions, and experimental constraints.

For example, it has been found that PNA is a better charge conduit than DNA, and the flexible (thus, subject to larger fluctuations) PNA form is a better charge conduit than a rigid (methylated) PNA form. Surprisingly, we found that the conductance of flexible PNA is improved by the larger fluctuations of the PNA backbone and the associated electric field, rather than by the fluctuations of the nucleobase stack through which the charge is actually conducted. Fluctuations of one part of the molecule affect conductance through another part, isn't that great?!

Ultimately, understanding the molecular electronic properties will lead to new molecular designs for solar energy harvesting, molecular sensing, molecular synthesis and repair, and even the design of "smart" microorganisms enhanced by molecular "brains" based on macromolecular electronic circuits.

(PNA: a biomimetic cross between protein and DNA, a polymer that consists of nucleobases attached to a peptide backbone. Flexible, not burdened by the backbone electric charge, and a better conduit of the electric charge than DNA!)

Biomolecular Structure and Dynamics under Applied Forces

We are trying to understand how applied forces change macromolecular structure and dynamics. When the force is applied (either by an experimentalist or due to molecular interactions in the living cell), how does the molecular structure change? what interactions are responsible for molecular resistance to the applied force? could the applied forces turn on/off the electric current through the molecule? The current studies focus on the forced extension of single- and double-stranded nucleic acids. A stunning discovery revealed that stretched DNA adapts an unusual form called zip-DNA which evolves through a disordered DNA state, is predicted to have a better conductivity per unit length than the B-form DNA, and potentially abolishes a fundamental structure-sequence relation in DNA.